Angiotensin receptor blocker neprilysin inhibitors

Abstract

Heart failure (HF) is a clinical syndrome that results from a structural or functional cardiac disorder that reduces the ability of the ventricle of the heart to fill with, or eject, blood. It is a multifaceted clinical condition that affects up to 2% of the population in the developed world, and is linked to significant morbidity and mortality; it is therefore considered a major concern for public health. Regarding the mechanism of HF, three neurohumoral factors - the renin-angiotensin-aldosterone system, the sympathetic nervous system, and natriuretic peptides - are related to the pathology of chronic HF (CHF), and the targets of treatment. Angiotensin receptor blocker and neprilysin inhibitor (angiotensin-receptor neprilysin inhibitor), namely sacubitril/valsartan (SAC/VAL), has been introduced as a treatment for CHF. SAC/VAL is an efficacious, safe, and cost-effective therapy that improves quality of life and longevity in patients with HF with reduced ejection fraction (HFrEF), and reduces hospital admissions. An in-hospital initiation strategy offers a potential new avenue to improve the clinical uptake of SAC/VAL. In the last five years, SAC/VAL has been established as a cornerstone component of comprehensive disease-modifying medical therapy in the management of chronic HFrEF. On the other hand, further work, with carefully designed and controlled preclinical studies, is necessary for understanding the molecular mechanisms, effects, and confirmation of issues such as long-term safety in both human and animal models.

Keywords: Angiotensin receptor blocker and neprilysin inhibitor; Chronic heart failure; Natriuretic peptide; Renin-angiotensin-aldosterone-system; Sacubitril/valsartan; Sympathetic nervous system.

Figure 1

Three neurohumoral factors related to the pathology of chronic heart failure, and the targets of conventional remedies. ACEI: Angiotensin-converting enzyme inhibitors; ARB: Angiotensin receptor blockers; BB: β-blocker; BP: Blood pressure; HF: Heart failure; HR: Heart rate; MRA: Mineralocorticoid receptor antagonist; RAAS: Renin-angiotensin-aldosterone-system.

Figure 2

Mechanism of sacubitril/valsartan on heart failure progression. AT1: Angiotensin II type 1; HF: Heart failure; NP: Natriuretic peptide; RAAS: Renin-angiotensin-aldosterone-system; SAC/VAL: Sacubitril/valsartan.

Figure 3

The therapeutic options and treatment lines of patients with symptoms of heart failure with reduced ejection fraction. ACEI: Angiotensin-converting enzyme inhibitor; AF: Atrial fibrillation; ARB: Angiotensin receptor blocker; ARNI: Angiotensin receptor neprilysin inhibitor; BB: β-blocker; bpm: Beats per minute; CRT: Cardiac resynchronization therapy; HR: Heart rate; ICD: Implantable cardioverter defibrillator; LVEF: Left ventricular ejection fraction; MRA: Mineralocorticoid receptor antagonist; NYHA: New York Heart Association; SR: Sinus rhythm.